Carcinomas produce large amounts of
prostaglandin (PG) E2, which play an important role in suppression of non-specific cellular immune reaction in
tumor-bearing individuals. PG synthesis inhibitor can restore the immune activity against
tumors. The anti-
tumor activity of
indomethacin was investigated in CDF1 mice (BALB/c X DBA/2) implanted intraperitoneally with mouse
colon adenocarcinoma 26 (5 X 10(5) or 2 X 10(5) cells) in a model study to prevent peritoneal recurrence after surgery for
gastrointestinal cancers.
Oral administration of
indomethacin (0.002% water
solution as
drinking water) depressed and inhibited the disseminated
tumor growth in the abdominal cavity, and prolonged the survival time, resulting in 30-50% cures of mice. The treatment combined with a small intraperitoneal dose of
Picibanil (OK-432) (0.5 mg/kg twice weekly), which activates macrophages in the abdominal cavity, cured 90% of mice. An intraperitoneal dose of
16,16-dimethyl-PGE2 (5 micrograms/mouse, daily) reduced the anti-
tumor activity of
indomethacin. The results suggest that
indomethacin treatment relieved the endogenous(
tumor cell- and macrophage-produced) PGE2-mediated immunosuppression. It is postulated that PG-synthesis inhibitor in combination with chemotherapeutic agents, immunotherapeutic agents and low dose radiation, may provide a good therapeutic tool to prevent the development of
peritoneal carcinomatosis, particularly in the cases having a small number of
residual cancer cells or
micrometastases in the abdominal cavity after surgery.